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Infection and Immunity, August 2002, p. 4059-4067, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4059-4067.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Microarray-Based Identification of htrA, a Streptococcus pneumoniae Gene That Is Regulated by the CiaRH Two-Component System and Contributes to Nasopharyngeal Colonization

M. E. Sebert,1 L. M. Palmer,2 M. Rosenberg,2 and J. N. Weiser3*

Department of Pediatrics, Children’s Hospital of Philadelphia,1 Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104,3 Antimicrobials and Host Defense CEDD, GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania 194262

Received 13 February 2002/ Returned for modification 25 April 2002/ Accepted 9 May 2002

Nasopharyngeal carriage is the reservoir from which most disease with Streptococcus pneumoniae arises. Survival as a commensal in this environment is likely to require a set of adaptations distinct from those needed to cause disease, some of which may be mediated by two-component signal transduction systems (TCSTS). We examined the contributions of nine pneumococcal TCSTS to the process of nasopharyngeal colonization by using an infant rat model. Whereas deletions in all but one of these systems have been associated previously with a high degree of attenuation in a murine model of pneumonia, only the CiaRH system was necessary for efficient carriage. Transcriptional analysis by using microarray hybridization identified a locus consisting of two adjacent genes, htrA and spoJ, that was specifically and strongly downregulated in a {Delta}ciaRH-null mutant. A S. pneumoniae strain lacking the htrA gene encoding a putative serine protease, but not one lacking spoJ, showed decreased fitness in a competitive model of colonization, a finding consistent with this gene mediating a portion of the carriage deficit observed with the {Delta}ciaRH strain.

* Corresponding author. Mailing address: 402A Johnson Pavilion, Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104-6076. Phone: (215) 573-3511. Fax: (215) 898-9557. E-mail: weiser{at}mail.med.upenn.edu.

Editor: E. I. Tuomanen

Infection and Immunity, August 2002, p. 4059-4067, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4059-4067.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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